Collaborative Research: PurSUiT: Systematic viral discovery through structured search of host phylogeny

病毒性病原体在出现并在人类或家畜中引起疾病后，通常会进行深入研究。这导致了对影响人类的少数病毒的深刻理解，但在很大程度上忽略了其他哺乳动物中未知的大量病毒多样性。该项目利用自然历史博物馆中保存的高质量、低温冷冻的野生哺乳动物组织，系统地对哺乳动物生命之树的病毒多样性进行测序、发现和表征。该项目将直接有助于了解宿主-病毒的进化，了解“溢出”或宿主切换可能发生的频率和距离，并确定高风险和低风险的病毒病原体。通过将病毒序列与博物馆的物理哺乳动物标本相连接，该项目为未来详细调查特定病原体、病原体群落及其哺乳动物宿主的相关遗传变异提供了基础。为了进一步加强微生物研究与自然历史博物馆之间的联系，该项目将与ECHO项目的美洲博物馆和新发病原体（MEPA）网络合作，促进国际思想交流，并在更有可能出现病原体的生物多样性国家开展能力建设。该项目使用一种采样策略，优化进化距离和地理覆盖范围，选择哺乳动物标本进行病毒调查。最初，将以27目中25目近600种哺乳动物为核心样本，对哺乳动物的病毒多样性进行全面调查。基于这一初步努力，将选择具有特别丰富的病毒群落的谱系进行更密集的采样，以便分析病毒-病毒相互作用和宿主-病毒共同进化（或缺乏）。新的和已知的病毒序列将被生物信息学地重建，并用于测试与病毒多样性、宿主特征和宿主多样性有关的长期假设，包括哪些谱系对人类代表“高风险”或“低风险”（例如，蝙蝠、啮齿动物和灵长类动物传统上是“高风险”群体）。对显示宿主转换率升高的哺乳动物和病毒谱系将用于确定与此类事件相关的生态和环境特征。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Viral pathogens are usually researched intensively after they emerge and cause disease in humans or domestic animals. This leads to a deep understanding of the few viruses that affect humans, but largely ignores the vast, unknown diversity of viruses in the rest of mammals. This project leverages the high-quality, cryogenically frozen tissue collections of wild mammals that are stored in natural history museums to systematically sequence, discover, and characterize viral diversity from across the Mammal Tree of Life. This project will contribute directly to the understanding of host-virus evolution, inform the frequency and distance at which ‘spillover’ or host-switches can occur, and identify high and low risk viral pathogens. By connecting the viral sequences back to a physical mammal specimen at a museum, this project provides a foundation for detailed future investigations of specific pathogens, pathogen communities, and the associated genetic variation in their mammal hosts. To further reinforce the connection between microbial research and natural history museums, this project will collaborate with Project ECHO’s Museums and Emerging Pathogens in the Americas (MEPA) network to foster international exchange of ideas and build capacity in biodiverse countries, where pathogen emergence is more likely. This project uses a sampling strategy that optimizes evolutionary distances and geographic coverage to select mammal specimens to survey for viruses. Initially, a core set of nearly 600 mammalian species in 25 of 27 orders will be targeted to provide a mammal-wide survey of viral diversity. Based on this initial effort, lineages that have especially rich viral communities will be selected for more intensive sampling that will allow for analyses of virus-virus interactions and host-virus co-evolution (or lack thereof). New and known viral sequences will be reconstructed bioinformatically and used to test long-standing assumptions related to viral diversity, host traits, and host diversity, including which lineages represent “high risk” or “low risk” to humans (e.g., bats, rodents, and primates as traditionally “high risk” groups). Pairs of mammal and virus lineages that show elevated rates of host switching will be used to identify the ecological and environmental traits that are associated with such events.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.